Avian limb outgrowth and morphogenesis is under the control of a complex set of interactions, both between and within tissue components. The ectodermal ridge is known to be necessary for continued limb outgrowth but the asymmetry of its thickness and therefore, probably its inductive activity, is under the control of, and is maintained by, the mesoderm. The pattern of maintenance in the mesoderm (decreasing in activity anteriorly in gradient fashion) is thus reflected in the ectodermal ridge and therefore in outgrowth under the ridge's influence. This pattern of mesodermal maintenance seems to be under the control of yet another region of the limb mesoderm, the zone of polarizing activity, which under appropriate experimental conditions will induce limb outgrowth and determine a morphogenetic pattern - the anteroposterior polarity of the induced limb. The object of this proposed research is to investigate the mechanisms involved in these interactions using mutants with disrupted morphogenetic patterns, as well as normal limb material. In addition, investigations will begin into the chemical nature of polarizing activity, using an in vitro assay recently developed in this laboratory. Finally, investigations aimed at discovering whether similar interactions are controlling the outgrowth and morphogenetic patterns of the mammalian limb will be initiated.